Hepatic encephalopathy is a complication that is often observed when a hepatic malfunction such as liver cirrhosis, fulminant hepatic failure and the like occurs, and presents various psychoneurosis symptoms. As an early indication of the encephalopathy, such symptoms appear that self-control is not exercised, hypnic rhythm is disturbed, or day and night are mixed up. Subsequently, judgement is lowered and the patient becomes confused, and finally, the patient lapses into a coma and cannot react to an external stimulus.
As to one cause of hepatic encephalopathy, it is taken very seriously that ammonia generated mainly by means of bacteria in an intestine is absorbed into the liver, is not detoxicated therein and is transferred to the brain. Therefore, administration of antibiotics in order to remove the bacteria in the intestine, or administration of lactulose for absorption restraint of ammonia and the like (Japanese Patent Laid-open No. Hei. 10-158172 etc.) is conventionally carried out. However, the efficacy of these treatments is not yet sufficient.
Furthermore, as to other causes, an imbalance of the free amino acids in the blood plasma is noted such that a concentration of aromatic amino acids comprising L-phenylalanine, L-tryptophan, L-tyrosine and the like in the plasma is increased while a concentration of branched amino acids comprising L-leucine, L-isoleucine, L-valine and the like is decreased with severe hepatopathy. This imbalance of the free amino acids in the blood plasma causes an abnormality of amino acid metabolism in the brain such as an abnormality in transporting amino acids into the brain across the blood brain barrier, an inhibition of normal production of neurotransmitters in the brain, and production of pseudo-neurotransmitters. Therefore, there is a view that hepatic encephalopathy is caused.
Therefore, administration of an amino acid preparation containing a large amount of branched amino acids and a reduced amount of aromatic amino acids is carried out as a new treatment (Japanese Examined Patent Publication No. Hei. 3-28403, Japanese Laid-open Patent No. 1-83017, and Japanese Patent Laid-open No. Hei. 3-127737). A preparation comprising such a composition is commercialized as a therapeutic agent for hepatic encephalopathy (JJPEN, 11(9), 1137, 1989). However, this amino acid preparation shows a therapeutic effect of only about 46% on hepatic encephalopathy caused by an acute hepatic insufficiency, and the efficacy is not sufficient (Shin-yaku to Rinsho, 31, 175-185, 1982).
Alternatively, the inventors of the present invention had an idea that if albumin is supplied and a concentration of albumin in the blood is restored on affecting such hepatopathy, amino acids administered as an amino acid preparation will not be consumed for albumin synthesis and the state of an amino acid imbalance will smoothly improve, and as a result, abnormality of amino acid metabolism occurring in the brain with hepatic encephalopathy can be improved rapidly.
An object of the present invention is to provide an amino acid preparation for preventing an onset of hepatic encephalopathy caused by a conventional amino acid preparation and enhancing an effect of amelioration of the symptoms.